lunes, 9 de julio de 2018

Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing. - PubMed - NCBI

2018 Jun 28. pii: haematol.2018.188839. doi: 10.3324/haematol.2018.188839. [Epub ahead of print]

Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing.

Ruiz-Heredia Y1, Sànchez-Vega B1, Onecha E1, Barrio S2, Alonso R3, Martínez-Ávila JC4, Cuenca I1, Agirre X5, Braggio E6, Hernández MT7, Martínez R8, Rosiñol L9, Gutierrez N10, Martin-Ramos M3, Ocio EM10, Echeveste MA11, Pérez de Oteyza J12, Oriol A13, Bargay J14, Gironella M15, Ayala R16, Bladé J17, Mateos MV10, Kortum KM18, Stewart K6, García-Sanz R10, San Miguel J5, Lahuerta JJ19, Martinez-Lopez J20.

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Abstract

Next-generation sequencing has substantially improved our understanding of the genomic landscape of multiple myeloma; however, the application of this technology has been confined mostly to research studies. Here, we report on a customized panel to characterize the mutational profile of 79 newly diagnosed patients with multiple myeloma, older than 65 years and who were not transplant candidates, applying the highest read depth to date that has been used for equivalent studies in multiple myeloma. Overall, we identified 53 genes mutated in 85% of patients, including KRAS, NRAS, BRAF, DIS3 and TP53, and found a complex subclonal structure. In addition, the total number of mutations, as well as mutations in TP53 and the Cereblon pathway, were negatively associated with survival. The latter result is particularly noteworthy as patients enrolled in this phase II clinical trial were treated with lenalidomide, which targets this pathway. Our next-generation sequencing strategy not only identified a group of patients with poor outcome, but also provided an extensive genetic profile that should prove useful in the search for new biomarkers and therapeutic targets in multiple myeloma, at an affordable price and with a small amount of sample, which are indispensable features for translating personalized medicine protocols to clinical practice.